Significance of biopterin induction in rats with postburn Staphylococcus aureus sepsis

摘要

Objective: It has been demonstrated that biopterin, an essential cofactor of nitric oxide synthase (NOS), plays an important role in the pathogenesis of endotoxin-induced shock, yet its biological significance in gram-positive sepsis remains unclear. In this study, we adopted a rat model of postburn Staphylococcus aureus (S.aureus) sepsis to observe the time course and tissue distribution of biopterin in postburn S. aureus infection, and to investigate its potential role in the pathogenesis of gram-positive sepsis. Wistar rats were inflicted with a 20% total body surface area (TBSA) full-chickness scald injury followed by S. aureus challenge, then guanosine triphosphatecyclohydrolase I (GTP-CHI) mRNA expression and biopterin levels in liver, kidneys, lungs and heart were determined at 0. 5, 2, 6, 12 and 24 hours after S. aureus challenge. We found that after S. aureus challenge, GTP-CHI gene expressions and biopterin levels were markedly up-regulated in various tissues, and remained at high values up to 24 hours (P＜ 0. 05-0.01). Meanwhile, the organ function indexes, including serum alanine amimotransferase (ALT), aspartate aminotransferase (AST), creatinine (Cr), MB isoenzyme of creatine kinase (CK-MB), levels and pulmonary myeloperoxidase (MPO) activities significantly increased at 24 hours postburn, and the multiple organ dysfunction was aggravated by S. aureus challenge. Moreover, it was shown that cardiac GTP-CHI mRNA expression and renal BH4levels were positively correlated with CK-MB and Cr (r=0. 892, P=0. 0012 and r=0. 9423,P=0.0015, respectively). Conclusion: These results suggested that thermal injury combined with S. aureus challenge could induce de novo biosynthesis of biopterin, which acts as the most important cofactor of iNOS, might play a role in the development of multiple organ dysfunction syndrome secondary to postburn sepsis.